A New Age in Alzheimer’s Research

With technological advances in medicine, researchers are testing modifiable lifestyle factors, groundbreaking vaccines, and preventative drugs for Alzheimer’s disease—giving new hope for future generations.

By Morgan Stephens Photos: Courtesy of Keck Medicine of USC

Alzheimer’s disease is the only top 10 cause of death in the United States that cannot be prevented, cured or even slowed, although this bleak fact could soon be changing. Recent discoveries in Alzheimer’s disease at Keck School of Medicine of University of Southern California have researchers optimistic that breakthroughs in preventing or slowing the disease are soon within reach.

Until this new era of technological developments, the scope of a diagnosis could only go as far as “probable Alzheimer’s” or waited to be officially diagnosed at an autopsy. Today, with amyloid PET scans and brain imaging, researchers can examine the brain pathology of Alzheimer’s disease, at last discovering the mysteries of how Alzheimer’s progresses in patients.

One in three senior citizens age 65 and older die with Alzheimer’s or another dementia. Today, it is the sixth leading cause of death in the US, with 5.5 million people currently living with the disease. The earliest general symptoms of Alzheimer’s are problems with memory—episodic memory in particular—with long-term memories of childhood generally spared. Among other symptoms, unknowingly repeating oneself, losing things, lack of attention, challenges with driving and problems with direction, are common.

Approaching an Elusive Disease:

Often patients and their families are left with many concerns after an Alzheimer’s diagnosis. Such as “What options do I have? Which medications are available? Is there ever a point where intervention is limited—or even unattainable?” Judy Pa, assistant professor at the Institute for Neuroimaging and Informatics at Keck School of Medicine helps to answer these questions.

“I think it depends on what the goals are at different stages,” Pa says. “When they are no longer able to take care of themselves, pay bills, cook, and when they really lose their instrumental activities of daily living like dressing themselves, brushing their teeth, feeding themselves- basic human behaviors- even at those stages goals just change. Early on you want to preserve cognition. You want Mom to remember her kids and grandchildren, but once an individual gets to that [severely impaired] stage, it changes. So, you want to maintain quality of life. You want to reduce agitation and anxiety.”

A common misconception is that you can’t do anything about Alzheimer’s disease, according to Pa. Her current five-year study, LEARNIt (Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial) is considering how physical and cognitive activity affect brain pathology in older adults with elevated risk of Alzheimer’s. LEARNIt randomly selects its participants to commit to 150 minutes per week of either physical activity—light aerobic exercise, or cognitive activity—reading about lifestyle factors that are important for aging, for a full six months. Pa then compares the differences of how the two types of intervention strategies affect brain health, cognition and physical function. Now, two years into the study, she is seeing how these lifestyle factors influence the probability of developing Alzheimer’s disease or increase cognitive decline in those already living with the disease.

Pa also considers lack of social engagement as another factor that can influence Alzheimer’s disease. “One of the problems with older adults is, as they age, they become more socially isolated. Friends start to die. Their children have moved away. They may spend eight hours watching TV and living a sedentary lifestyle. Not going out and taking a walk, or going downstairs to play bridge or cards can affect this...and so we know that socialization is definitely a risk factor as well.”

Natural Memory Loss versus Alzheimer’s Disease:

It should be noted that with natural aging comes moderate memory loss. It’s important to consider the difference between dementia and Alzheimer’s.

“Dementia and Alzheimer's are two related but distinct concepts. Dementia is not a specific diagnosis. It’s a description of the problem. It occurs in typically elderly people and to a degree, impacts the activities of daily living. Dementia has many causes…Alzheimer's is the most common cause,” says Professor of Clinical Neurology at Keck School of Medicine John Ringman.

Ringman specializes in Alzheimer’s and has devoted much of his career studying families of the rare early onset Alzheimer’s disease Jalisco, a gene-mutation affecting 1 percent of individuals from mostly Mexico and Puerto Rico. This gene mutation affects adults as early as 40 years old, and is passed down directly from generation to generation.

The root cause of Alzheimer’s has yet to be discovered due to the complexity of how the disease develops in the brain. According to Ringman, patients typically go from what we consider normal to severely impaired in four to 12 years. For patients and their families, being able to distinguish between memory loss common with aging and Alzheimer’s disease is important.

“Normal changes of cognition in aging differentiating them from early Alzheimer's can be tricky,” says Ringman. “A gross example I use is, I don't get worried about people who lose their car keys, I get worried about people who lose their car.”

Understanding Plaques and Tangles:

Although researchers are still not sure what causes Alzheimer’s, proteins such as plaques and tangles are viewed as the catalysts in cell death and tissue loss in the brain. Before symptoms are present to patients and their families, these distinct pathological changes seem to materialize.

The scientific consensus is that beta-amyloid peptide - a sticky glue-like protein deposit in the brain- is the first signs of Alzheimer’s development. These plaques are abnormal clusters that build up between nerve cells. Amyloid plaques can develop 10 to 15 years before any symptoms of the disease appear, and seem to be the key to prevention development.

“We have great new tools for studying the earliest molecular changes of Alzheimer's disease,” says Senior Author and Director of USC Alzheimer’s Therapeutic Research Institute at Keck School of Medicine Paul Aisen. As the leading figure in Alzheimer’s research for more than two decades, Aisen helped develop the earliest Alzheimer’s medications patients still use today.

“This gives us a highly promising strategy for developing effective treatment,” he says. “We do have treatments today and they do help, but they don't change the course of the disease. They only offer modest relief of symptoms. We can do much better than that and we think that the most promising strategy is to focus on this amyloid peptide.”

Tau protein, the other facet to decoding the Alzheimer’s mystery, forms into neurofibrillary tangles in the brain shortly after amyloid growth accumulates. These tangles cultivate in brains areas important for memory then spread over time. Scientists believe tau development represents the beginning stage of symptomatic Alzheimer’s.

Although it’s imperative to note that a positive amyloid PET scan does not signify that one will absolutely get Alzheimer’s. “You wouldn’t want to diagnose someone based on an amyloid scan…Many people will grow old and die with a positive amyloid pet scan and not have Alzheimer's disease,” says Professor of Psychiatry and Neurology at Keck School of Medicine and Director of California’s Alzheimer’s Disease Center Lon Schneider.

Schneider is in the process of conducting an eight-year prevention study to develop an amyloid vaccine in adult’s who have a substantial risk of developing the disease from their genetic disposition.

“We're taking people who don't have symptoms at all. They don't necessarily have a positive amyloid pet scan but do carry the APOE-4 gene, which gives them a higher risk of developing Alzheimer's disease,” says Schneider. “We're using an anti-amyloid vaccine, essentially. Injecting particles of synthetic amyloid to cause antibodies against amyloids. We hope that the series of vaccines—essentially booster shots—will create enough antibodies that it will endogenously remove amyloid on its own when it's forming.”

This study comes with its own set of challenges. The recruitment pool, those who possess two copies of the APOE-4 gene represent only 3 percent of the population. According to Schneider, it could take up to 12 years to recruit participants, conduct the study, and then if all goes as planned, get FDA approval and sent out on the market.

With Great Power Comes Great Responsibility:

Numerous prevention and treatment trials for the disease are actively recruiting adults with focus on reducing Alzheimer’s symptoms and slowing or stopping the disease. Individuals with or without dementia are encouraged to participate. By doing so, the public can provide valuable insight into potential treatments for Alzheimer’s patients today and for future generations.

“Without the generous participation of volunteers in our studies, we cannot develop effective treatment. If more people join our effort in participating in clinical research it would accelerate our work,” says Aisen.

These technological breakthroughs in medicine being achieved at Keck Medicine of USC have given researchers the gift of crucial discoveries that they needed for helping current and future Alzheimer’s patients struggling with a debilitating disease. This brings a renewed sense of hope for finding methods for prevention, or even a possible cure down the road.

“While we've been working on this disease for a long time and don't yet have highly effective approved drugs, we're getting very close,” says Aisen. “We're very excited about studies that are underway or are just getting started. We think that with the coming years, we are going to bring substantial advancement so there is a very hopeful, upbeat view in the field right now.”